Sohair R. Fahmy

Bio: Sohair R. Fahmy is an academic researcher from Cairo University. The author has contributed to research in topics: Creatinine & Medicine. The author has an hindex of 17, co-authored 49 publications receiving 628 citations.

Curcumin-Loaded Solid Lipid Nanoparticles Bypass P-Glycoprotein Mediated Doxorubicin Resistance in Triple Negative Breast Cancer Cells.

Abstract: Multidrug resistance (MDR) is a critical hindrance to the success of cancer chemotherapy. The main thing responsible for MDR phenotypes are plasma-membranes associated with adenosine triphosphate (ATP) Binding Cassette (ABC) drug efflux transporters, such as the P-glycoprotein (Pgp) transporter that has the broadest spectrum of substrates. Curcumin (CURC) is a Pgp inhibitor, but it is poorly soluble and bioavailable. To overcome these limitations, we validated the efficacy and safety of CURC, loaded in biocompatible solid lipid nanoparticles (SLNs), with or without chitosan coating, with the goal of increasing the stability, homogeneous water dispersibility, and cellular uptake. Both CURC-loaded SLNs were 5-10-fold more effective than free CURC in increasing the intracellular retention and toxicity of doxorubicin in Pgp-expressing triple negative breast cancer (TNBC). The effect was due to the decrease of intracellular reactive oxygen species, consequent inhibition of the Akt/IKKα-β/NF-kB axis, and reduced transcriptional activation of the Pgp promoter by p65/p50 NF-kB. CURC-loaded SLNs also effectively rescued the sensitivity to doxorubicin against drug-resistant TNBC tumors, without signs of systemic toxicity. These results suggest that the combination therapy, based on CURC-loaded SLNs and doxorubicin, is an effective and safe approach to overcome the Pgp-mediated chemoresistance in TNBC.

Protective and Curative Effects of the Sea Cucumber Holothuria atra Extract against DMBA-Induced Hepatorenal Diseases in Rats

Abstract: Oxidative stress is a common mechanism contributing to the initiation and progression of hepatic damage. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present study is to evaluate the efficacy of Holothuria atra extract (HaE) as an antioxidant against 7,12-dimethylbenz[a]anthracene- (DMBA-) induced hepatorenal dysfunction. Experimental animals were divided into two main groups: protective and curative. Each group was then divided into five subgroups pre- or posttreated either with distilled water (DMBA subgroups) or with HaE (200 mg/kg body weight) for seven and fourteen days. Single oral administration of DMBA (15 mg/kg body weight) to Wistar rats resulted in a significant increase in the serum liver enzymes and kidney function's parameters. DMBA increased level of liver malondialdehyde (MDA), decreased levels of reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) in the liver tissue, and induced liver histopathological alterations. Pre- or posttreatment with HaE orally for 14 days significantly reversed the hepatorenal alterations induced following DMBA administration. In conclusion, HaE exhibits good hepatoprotective, curative, and antioxidant potential against DMBA-induced hepatorenal dysfunction in rats that might be due to decreased free radical generation.

Toxicological effects of zinc oxide nanoparticles: Ecotoxicological effect of sublethal exposure to zinc oxide nanoparticles on freshwater snail Biomphalaria alexandrina

Abstract: Freshwater snails are used as sensitive biomarkers of aquatic ecosystem pollution. The potential impacts of zinc oxide nanoparticles (ZnONPs) on aquatic ecosystems have attracted special attention due to their unique properties. The present investigation was designed to evaluate the possible mechanisms of ecotoxicological effects of ZnONPs on freshwater snail Biomphalaria alexandrina. ZnONPs showed molluscicidal activity against B. alexandrina snails, and the LC50 was 145 μg/ml. Two tested concentrations of ZnONPs were selected: The first concentration was equivalent to LC10 (7 μg/ml), and the second was equivalent to LC25 (35 μg/ml). Exposure to ZnONPs (7 and 35 μg/ml) for three consecutive weeks significantly induced malondialdehyde and nitric oxide with concomitant decreases in glutathione and glutathione-S-transferase levels in hemolymph and soft tissues of treated snails. Moreover, ZnONPs elicited a significant decrease in total protein and albumin contents coinciding with enhancement of total lipids and cholesterol levels as well as activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in hemolymph and soft tissues of treated snails. This study highlights the potential ecological implications of ZnONP release in aquatic environments and may serve to encourage regulatory agencies in Egypt to more carefully monitor and regulate the industrial use and disposal of ZnONPs.

Ecotoxicological Effect of Sublethal Exposure to Zinc Oxide Nanoparticles on Freshwater Snail Biomphalaria alexandrina

Abstract: Freshwater snails are used as sensitive biomarkers of aquatic ecosystem pollution. The potential impacts of zinc oxide nanoparticles (ZnONPs) on aquatic ecosystems have attracted special attention due to their unique properties. The present investigation was designed to evaluate the possible mechanisms of ecotoxicological effects of ZnONPs on freshwater snail Biomphalaria alexandrina. ZnONPs showed molluscicidal activity against B. alexandrina snails, and the LC50 was 145 μg/ml. Two tested concentrations of ZnONPs were selected: The first concentration was equivalent to LC10 (7 μg/ml), and the second was equivalent to LC25 (35 μg/ml). Exposure to ZnONPs (7 and 35 μg/ml) for three consecutive weeks significantly induced malondialdehyde and nitric oxide with concomitant decreases in glutathione and glutathione-S-transferase levels in hemolymph and soft tissues of treated snails. Moreover, ZnONPs elicited a significant decrease in total protein and albumin contents coinciding with enhancement of total lipids and cholesterol levels as well as activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in hemolymph and soft tissues of treated snails. This study highlights the potential ecological implications of ZnONP release in aquatic environments and may serve to encourage regulatory agencies in Egypt to more carefully monitor and regulate the industrial use and disposal of ZnONPs.

Hazardous effects of acrylamide on immature male and female rats

Abstract: Acrylamide (ACR) is an industrial chemical which induces neurotoxic effects in experimental animals and humans. The present study was carried out to investigate the hematological, biochemical, neurological and histopathological effects of ACR on immature male and female rats. Animals were divided into 2 main groups; immature male group and immature female group and all rats were treated for 28 consecutive days. Each main group subsequently was divided into 2 subgroups: (I) Untreated control group that received a daily oral administration of distilled water and (II) ACR treated rats which received a daily oral administration of ACR (15 mg/kg/body weight). The results obtained indicate that ACR administration induced some behavioral disorders in the movement of immature male and female rats as well as loss of body weight. ACR induced a significant decrease in hemoglobin (Hb), erythrocytes (RBCS), hematocrit (HCT) and lymphocyte levels of young female rats. ACR significantly increased serum glucose, total cholesterol and triglycerides concentrations of both immature male and female rats. While, significant increase in the total urea concentration was noticed only in the immature male rats following ACR administration. Moreover, ACR induced marked increase in the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the immature male and female rats. On the other hand, the activities of serum alkaline phosphatase (ALP) and acetylcholinesterase (AChE) were significantly decreased in both treated groups. ACR caused a significant increase in norepinephrin (NE), glutamate, aspartate and taurine, while it reduced dopamine (DA) and serotonin (5-HT) levels. In conclusion, the present study showed that, ACR induced hazardous effects on immature male and female rats. So, we recommended that children must avoid fast or junk foods. Key words: Acrylamide, hematological, biochemical, neurological. histopathological, immature.

The Role of Oxidative Stress and Antioxidants in Liver Diseases

Abstract: A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain), 2015. Scientific Opinion on acrylamide in food

Abstract: EFSA was asked to deliver a scientific opinion on acrylamide (AA) in food. AA has widespread uses as an industrial chemical. It is also formed when certain foods are prepared at temperatures above 120 °C and low moisture, especially in foods containing asparagine and reducing sugars. The CONTAM Panel evaluated 43 419 analytical results from food commodities. AA was found at the highest levels in solid coffee substitutes and coffee, and in potato fried products. Mean and 95th percentile dietary AA exposures across surveys and age groups were estimated at 0.4 to 1.9 μg/kg body weight (b.w.) per day and 0.6 to 3.4 μg/kg b.w. per day, respectively. The main contributor to total dietary exposure was generally the category ‘Potato fried products (except potato crisps and snacks)’. Preferences in home-cooking can have a substantial impact on human dietary AA exposure. Upon oral intake, AA is absorbed from the gastrointestinal tract and distributed to all organs. AA is extensively metabolised, mostly by conjugation with glutathione but also by epoxidation to glycidamide (GA). Formation of GA is considered to represent the route underlying the genotoxicity and carcinogenicity of AA. Neurotoxicity, adverse effects on male reproduction, developmental toxicity and carcinogenicity were identified as possible critical endpoints for AA toxicity from experimental animal studies. The data from human studies were inadequate for dose-response assessment. The CONTAM Panel selected BMDL10 values of 0.43 mg/kg b.w. per day for peripheral neuropathy in rats and of 0.17 mg/kg b.w. per day for neoplastic effects in mice. The Panel concluded that the current levels of dietary exposure to AA are not of concern with respect to non-neoplastic effects. However, although the epidemiological associations have not demonstrated AA to be a human carcinogen, the margins of exposure (MOEs) indicate a concern for neoplastic effects based on animal evidence. © European Food Safety Authority, 2015